Methods of predicting ancestral virus sequences and uses thereof

Abstract

Methods are described for predicting ancestral sequences for viruses or portions thereof. Also described are predicted ancestral sequences for adeno-associated virus (AAV) capsid polypeptides. The disclosure also provides methods of gene transfer and methods of vaccinating subjects by administering a target antigen operably linked to the AAV capsid polypeptides.

What is claimed is: 
     
       1. A method comprising:
 administering to a subject in need thereof a plurality of recombinant adeno-associated virus (rAAV) particles, wherein each rAAV particle comprises an AAV capsid polypeptide and a transgene, wherein the AAV capsid polypeptide comprises an amino acid sequence chosen from: SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, and 17, and the transgene is within the rAAV particle. 
 
     
     
       2. The method of  claim 1 , wherein the method is a method of vaccinating the subject. 
     
     
       3. The method of  claim 1 , wherein the method is a method of delivering a gene therapy to the subject. 
     
     
       4. The method of  claim 1 , wherein the AAV capsid polypeptide exhibits less seroprevalence than an AAV2 capsid polypeptide and/or about the same or less seroprevalence than an AAV8 capsid polypeptide. 
     
     
       5. The method of  claim 1 , wherein the AAV capsid polypeptide is neutralized to a lesser extent by human serum than an AAV2 capsid polypeptide, and wherein the AAV capsid polypeptide is neutralized to a similar or lesser extent by human serum than an AAV8 capsid polypeptide. 
     
     
       6. The method of  claim 1 , wherein the AAV capsid polypeptide has the sequence of SEQ ID NO: 1. 
     
     
       7. The method of  claim 1 , wherein the subject is a human. 
     
     
       8. The method of  claim 1 , wherein the plurality of rAAV particles are in a composition further comprising a carrier. 
     
     
       9. The method of  claim 1 , wherein the plurality of rAAV particles transduces or infects cells in the subject. 
     
     
       10. The method of  claim 9 , wherein the cells are ear cells. 
     
     
       11. The method of  claim 10 , wherein the ear cells are inner ear cells. 
     
     
       12. The method of  claim 4 , wherein the subject has a lower titer of antibodies that are capable of neutralizing the AAV capsid polypeptide than the titer of antibodies capable of neutralizing an AAV2 or AAV8 capsid polypeptide.